Macrocyclic Host Molecules Research Articles

The Swiss Army Knife of Electrodes: Pillar[6]arene-Modified Electrodes for Molecular Electrocatalysis Over a Wide pH Range.

Molecularly-modified electrode materials that maintain stability over a broad pH range are rare. Typically, each electrochemical transformation necessitates a specifically tuned system to achieve strong binding and high activity of the catalyst. Here, we report the functionalisation of mesoporous indium tin oxide (mITO) electrodes with the macrocyclic host molecule pillar[6]arene (PA[6]). These electrodes are stable within the pH range of 2.4-10.8 and can be equipped with electrochemically active ruthenium complexes through host-guest interactions to perform various oxidation reactions. Benzyl alcohol oxidation serves as a model reaction in acidic media, while ammonia oxidation is conducted to assess the systems performance under basic conditions. PA[6]-modified electrodes demonstrate catalytic activity for both reactions when complexed to different guest molecules and can be reused by reabsorption of the catalyst after its degradation. Furthermore, the system can be employed to perform subsequent reactions in electrolyte with varying pH, enabling the same electrode to be utilised in multiple different electrocatalytic reactions.

The Swiss Army Knife of Electrodes: Pillar[6]arene‐Modified Electrodes for Molecular Electrocatalysis Over a Wide pH Range

AbstractMolecularly‐modified electrode materials that maintain stability over a broad pH range are rare. Typically, each electrochemical transformation necessitates a specifically tuned system to achieve strong binding and high activity of the catalyst. Here, we report the functionalisation of mesoporous indium tin oxide (mITO) electrodes with the macrocyclic host molecule pillar[6]arene (PA[6]). These electrodes are stable within the pH range of 2.4–10.8 and can be equipped with electrochemically active ruthenium complexes through host–guest interactions to perform various oxidation reactions. Benzyl alcohol oxidation serves as a model reaction in acidic media, while ammonia oxidation is conducted to assess the systems performance under basic conditions. PA[6]‐modified electrodes demonstrate catalytic activity for both reactions when complexed to different guest molecules and can be reused by reabsorption of the catalyst after its degradation. Furthermore, the system can be employed to perform subsequent reactions in electrolyte with varying pH, enabling the same electrode to be utilised in multiple different electrocatalytic reactions.

Responsive Supramolecular Nanomicelles Formed through Self-Assembly of Acyclic Cucurbit[n]uril for Targeted Drug Delivery to Cancer Cells.

The supramolecular drug delivery systems (SDDSs) based on host-guest recognition through noncovalent interactions, capable of responsive behavior and dynamic switching to external stimuli, have attracted considerable attention in cancer therapy. In this study, a targeted dual-functional drug delivery system was designed and synthesized. A hydrophilic macrocyclic host molecule (acyclic cucurbit[n]uril ACB) was modified with folic acid (FA) as a targeting ligand. The guest molecule consists of a disulfide bond attached to adamantane (DA) and cannabidiol (CBD) at both ends of the response element of glutathione. Recognition and self-assembly of host and guest molecules successfully functionalize supramolecular nanomicelles (SNMs), targeting cancer cells and releasing drugs in a high glutathione environment. The interactions between host and guest molecules were investigated by using nuclear magnetic resonance (NMR), fluorescence titration, Fourier-transform infrared spectroscopy (FT-IR), and thermal analysis (TGA). Transmission electron microscopy (TEM) and dynamic light scattering (DLS) confirmed the nanostructure of the SNMs. Experimentation with 5,5'-dithiobis (2-nitrobenzoic acid) (DTNB) demonstrated the responsiveness of SNMs to glutathione (GSH). In vitro cytotoxicity assays demonstrated that SNMs had a greater targeting efficacy for four types of cancer cells (HeLa, HCT-116, A549, and HepG2) compared to normal 293T cells. Cellular uptake studies revealed that HeLa cells more readily absorbed SNMs, leading to their accumulation in the tumor cell cytoplasm. Fluorescence colocalization assays verified that SNMs efficiently accumulated in organelles related to energy metabolism and signaling, including mitochondria and the endoplasmic reticulum, affecting cellular metabolic death. Both flow cytometry and confocal nuclear staining assays confirmed that SNMs effectively induced apoptosis over time, ultimately resulting in the death of cancer cells. These findings demonstrate that SNMs exhibit excellent targeting ability, responsiveness, high bioavailability, and stability, suggesting significant potential in drug delivery applications.

Diameter-selective extraction of single-walled carbon nanotubes by interlocking with Cu-tethered square nanobrackets.

We have been working with carbon nanotube separation through host-guest chemistry. Herein, a new macrocyclic host molecule, Cu-tethered square nanobrackets, is designed, synthesized and applied to single-walled carbon nanotubes (SWNTs) for their diameter-based separation. The complexation between copper ions and dipyrrin moieties of the nanobracket gives Cu-tethered square nanobrackets, which is confirmed by absorption, Raman and MALDI-TOF mass spectra. Upon extraction of SWNTs with the nanobracket and copper(II), in situ-formed square Cu-nanobrackets are found to interlock SWNTs to disperse them in 2-propanol. The interlocking is confirmed by Raman spectroscopy after thorough washing of the extracted SWNTs. Pristine SWNTs were recovered through demetalation of the interlocked ones along with the nanobracket. Raman and absorption spectroscopies of the extracted SWNTs reveals the diameter enrichment of only several kinds of SWNTs in the diameter range from 0.94 to 1.10 nm among ≈20 kinds of SWNTs from 0.76 to 1.20 nm in their diameter range. The diameter selectivity is supported by the theoretical calculations with the GFN2-xTB method, indicating that the most preferred SWNT diameter for the square Cu-nanobrackets is 1.04 nm.

Recent advancements in encapsulation of poly aromatic hydrocarbons via macrocyclic host-guest chemistry

Polyaromatic hydrocarbons (PAHs) pose a significant threat to ecosystems and human health due to their widespread presence and persistence in the environment. Conventional remediation techniques often fall short in both efficiency and environmental impact. However, recent advancements in utilizing organic macrocyclic host molecules show considerable promise for effectively sequestering and eliminating PAHs across diverse media. These macrocyclic host molecules play a central role in host–guest chemistry and supramolecular chemistry. It offers distinct advantages by virtue of their precisely tailored cavities and customizable functionalities, greatly enhancing their selective recognition abilities towards guest PAHs. The pursuit of designing and synthesizing novel functional macrocycles has captivated the attention of researchers, driven by the quest to address various challenges in supramolecular research. Over decades of dedicated exploration in host–guest chemistry and supramolecular chemistry, an expansive array of macrocyclic host molecules, constructed from diverse building blocks, have emerged as pivotal tools for encapsulating PAHs. This review presents an overview of the recent progress in the design, synthesis, and application of purely organic macrocyclic molecules in the encapsulation of PAHs. It elucidates the underlying principles that govern their ability to recognise PAHs, such as host–guest interactions, shape complementarity, and π-π stacking interactions. Furthermore, the review discusses various experimental methodologies, such as spectroscopic analyses, chromatography, and computational modelling, employed to assess the efficiency of organic cage molecules in PAH trapping. Additionally, considerations regarding the scalability and environmental implications of organic cage-based PAH trapping systems are addressed. The insights gleaned from this research provide valuable guidance for the development of robust strategies to combat PAH pollution in diverse environmental contexts.

Pillar[n]arenes in the Fight against Biofilms: Current Developments and Future Perspectives.

The global surge in bacterial infections, compounded by the alarming escalation of drug-resistant strains, has evolved into a critical public health crisis. Among the challenges posed, biofilms stand out due to their formidable resistance to conventional antibiotics. This review delves into the burgeoning potential of pillar[n]arenes, distinctive macrocyclic host molecules, as promising anti-biofilm agents. The review is structured into two main sections, each dedicated to exploring distinct facets of pillar[n]arene applications. The first section scrutinizes functionalized pillar[n]arenes with a particular emphasis on cationic derivatives. This analysis reveals their significant efficacy in inhibiting biofilm formation, underscoring the pivotal role of specific chemical attributes in combating microbial communities. The second section of the review shifts its focus to inclusion complexes, elucidating how pillar[n]arenes serve as encapsulation platforms for antibiotics. This encapsulation enhances the stability of antibiotics and enables a controlled release, thereby amplifying their antibacterial activity. The examination of inclusion complexes provides valuable insights into the potential synergy between pillar[n]arenes and traditional antibiotics, offering a novel avenue for overcoming biofilm resistance. This comprehensive review highlights the escalating global threat of bacterial infections and the urgent need for innovative strategies to counteract drug-resistant biofilms. The unique properties of pillar[n]arenes, both as functionalized molecules and as inclusion complex hosts, position them as promising candidates in the quest for effective anti-biofilm agents. The exploration of their distinct mechanisms opens new avenues for research and development in the ongoing battle against bacterial infections and biofilm-related health challenges.

Synthesis and cooperative guest binding of tetrameric porphyrin macrocycle

AbstractA new family of macrocyclic host molecules that possess two bisporphyrin clefts was synthesized. The tetrameric porphyrin macrocycle provides the two guest binding sites in which two electron‐deficient aromatic molecules are encapsulated through donor‐acceptor and π‐π stacking interactions. The tetrameric porphyrin macrocycle showed positive cooperativity, whereas the nonmacrocyclic analog did not. The preorganization concept drives positive cooperativity, which is directed by the entropy benefit to macrocyclization.

Assembly and Utility of a Drawstring‐Mimetic Supramolecular Complex

AbstractInspired by the drawstring structure in daily life, here we report the development of a drawstring‐mimetic supramolecular complex at the molecular scale. This complex consists of a rigid figure‐of‐eight macrocyclic host molecule and a flexible linear guest molecule which could interact through three‐point non‐covalent binding to form a highly selective and efficient host‐guest assembly. The complex not only resembles the drawstring structure, but also mimics the properties of a drawstring with regard to deformations under external forces. The supramolecular drawstring can be utilized as an interlocked crosslinker for poly(methyl acrylate), and the corresponding polymer samples exhibit comprehensive enhancement of macroscopic mechanical performance including stiffness, strength, and toughness.

Assembly and Utility of a Drawstring-Mimetic Supramolecular Complex.

Inspired by the drawstring structure in daily life, here we report the development of a drawstring-mimetic supramolecular complex at the molecular scale. This complex consists of a rigid figure-of-eight macrocyclic host molecule and a flexible linear guest molecule which could interact through three-point non-covalent binding to form a highly selective and efficient host-guest assembly. The complex not only resembles the drawstring structure, but also mimics the properties of a drawstring with regard to deformations under external forces. The supramolecular drawstring can be utilized as an interlocked crosslinker for poly(methyl acrylate), and the corresponding polymer samples exhibit comprehensive enhancement of macroscopic mechanical performance including stiffness, strength, and toughness.

A guanidiniocarbonyl-pyrrole functionalized cucurbit[7]uril derivative as a cytomembrane disruptor for synergistic antibacterial therapy.

The antibiotic resistance of bacterial membranes poses a significant threat to global public health, highlighting the urgent need for novel therapeutic agents and strategies to combat bacterial membranes. In response, we have developed a novel macrocyclic host molecule (GCPCB) based on guanidiniocarbonyl-pyrrole (GCP) functionalized cucurbit[7]uril with an aggregation-induced luminescence effect. GCPCB exhibits high antimicrobial potency against bacterial membranes, particularly demonstrating strong antibacterial activity against Gram-positive strains of S. aureus and Gram-negative strains of E. coli. Significantly, due to the strong binding between GCP and the bacterial membrane, GCPCB can effectively eradicate the bacteria encapsulated within. Furthermore, the formation of a host-guest complex between GCPCB and berberine hydrochloride (BH) not only enhances synergistic destructive activity against both species of bacteria but also provides a potential supramolecular platform for effective bacterial membrane destruction.

Electrocatalytic Ammonia Oxidation with a Tailored Molecular Catalyst Heterogenized via Surface Host-Guest Complexation.

Macrocyclic host molecules bound to electrode surfaces enable the complexation of catalytically active guests for molecular heterogeneous catalysis. We present a surface-anchored host-guest complex with the ability to electrochemically oxidize ammonia in both organic and aqueous solutions. With an adamantyl motif as the binding group on the backbone of the molecular catalyst [Ru(bpy-NMe2)(tpada)(Cl)](PF6) (1) (where bpy-NMe2 is 4,4'-bis(dimethylamino)-2,2'-bipyridyl and tpada is 4'-(adamantan-1-yl)-2,2':6',2″-terpyridine), high binding constants with β-cyclodextrin were observed in solution (in DMSO-d6:D2O (7:3), K11 = 492 ± 21 M-1). The strong binding affinities were also transferred to a mesoporous ITO (mITO) surface functionalized with a phosphonated derivative of β-cyclodextrin. The newly designed catalyst (1) was compared to the previously reported naphthyl-substituted catalyst [Ru(bpy-NMe2)(tpnp)(Cl)](PF6) (2) (where tpnp is 4'-(naphthalene-2-yl)-2,2':6',2″-terpyridine) for its stability during catalysis. Despite the insulating nature of the adamantyl substituent serving as the binding group, the stronger binding of this unit to the host-functionalized electrode and the resulting shorter distance between the catalytic active center and the surface led to better performance and higher stability. Both guests are able to oxidize ammonia in both organic and aqueous solutions, and the host-anchored electrode can be refunctionalized multiple times (>3) following the loss of the catalytic activity, without a reduction in performance. Guest 1 exhibits significantly higher stability in comparison to guest 2 toward basic conditions, which often constitutes a challenge for anchored molecular systems. Ammonia oxidation in water led to the selective formation of NO3- with Faradaic efficiencies of up to 100%.

Calixarene-based supramolecular assembly with fluorescent gold-nanoclusters for highly selective determination of perfluorooctane sulfonic acid

The present study developed an efficient fluorescent approach, based on a supramolecular assembly between gold nanoclusters and calix[4]arene derivatives (C4A-Ds), to detect sever pollutant of perfluorooctane sulfonic acid (PFOS). For that, a series of C4A-Ds with different chain lengths and positive charges at the wider rim were designed and synthesized. Cytidine-5′ phosphate protected gold nanoclusters (AuNCs@CMP) were then assembled with calix[4]arene (LC4AP) to form AuNCs/LC4AP assembly, leading to 8-fold luminescence enhancement via the AIEE effect. However, further binding with PFOS reconstituted the as-formed assembly hrough a competitive effect, generating a fluorescence quenching. Particularly, the linear fluorescence response of AuNCs/LC4AP to PFOS realized a highly sensitive determination of the pollutant PFOS in a wide range (2.0–100 μM). In addition, the developed method successfully detected PFOS in pool water near a fire drill field, being good enough for the practical PFOS determination. The calixarene mediated method, based on the fluorescence “on–off” strategy of metal nanoclusters, is sensitive, rapid-responsive, economical, particularly, suitable for the PFOS determination in practice. It takes full advantage of the molecular recognition and self-assembly of artificial macrocyclic host molecules as a promising strategy for the PFOS determination, and will be highlight to develop new detection methods for PFOS and other poisonous compounds in environments.

Supramolecular nanoassemblies of rim-differentiated pillar[5]arene-rod-coil macromolecules via host-guest interactions for the sensing of cis-trans isomers of 1,4-diol-2-butene

Over the past few years, pillar[n]arene molecules have gained attention as novel functional materials due to their unique properties, including their pore size structure and exceptional host-guest capabilities. Among them, rim-differentiated pillar[5]arene is particularly favored for its unique asymmetric structure. In this study, we present a self-assembled macrocyclic host molecule (H1) based on a rim-differentiated pillar[5]arene unit and five rod-coil side chains containing a hepta (ethylene glycol) mono-methyl ether modified biphenyl and phenyl groups, which was self-assemble into 2D columnar nanostructures in the bulk state. It self-organizes into a double-layer vesicular aggregate when in a CHCl3 solution. The host-guest interactions between the nanoobjects and the guest molecule (G) composed of tetraphenylethene and hexanenitrile groups resulted in the construction of ordered nanostructures with good luminescent properties, such as lamellar nanostructure in the bulk state and a single-layer nanosheet in CHCl3 solution. This demonstrated that the morphology of the H1 can be manipulated by forming host-guest complexes, and by adjusting the intermolecular interactions between the molecules. Moreover, in the presence of cis-trans isomers of 1,4-diol 2-butene, we successfully separated and visually detected the trans isomers through competitive host guest interactions. This result not only provides a general approach for separating the cis-trans isomers of 1,4-diol 2-butene through supramolecular chemistry, but also sets a precedent for future research in this field.

Hydrogel Lasers Via Supramolecular Host–Guest Complexation

AbstractSupramolecular host–guest complexes are dynamic systems composed of typically macrocyclic host molecules encapsulating smaller guest molecules. One of their applications is the selective encapsulation of fluorescent dye molecules to tackle quenching and photobleaching in solution. When extended to solid matrices, the efficiency of dyes can be especially poor, limiting their use in fluorescence‐based applications. Here it is demonstrated that supramolecular host–guest complexation in a hydrogel network allows readily tunable hydrogel‐based lasers. Poly(N‐isopropylacrylamide)‐based copolymer hydrogel is used with covalently linked Rhodamine B molecules. By controlled doping of cucurbit[7]uril as a host molecule in the hydrogel, it is shown that the fluorescent quantum yield increases from 17% to 51%, accompanied by 15‐fold enhancement in photostability. As proof of concept, a thin‐film distributed feedback hydrogel laser with wavelength tunability is fabricated. The results reveal a 30% increase in slope efficiency in the presence of host molecules. These results, combined with the inherent stimuli‐response of hydrogels, enable new possibilities for affordable and small‐scale photonic devices capable of safely interacting with the environment in, for example, sensing applications.

An electrochemiluminescence insulin sensing platform based on the molecular recognition properties of cucurbit[7]uril

The establishment of new mechanisms for target identification and signal amplification continues to drive innovation in electrochemiluminescence (ECL) sensing platforms. In this paper, a novel ECL insulin sensing platform was constructed by utilizing the molecular recognition properties of cucurbit[7]uril. Specifically, the macrocyclic host molecule cucurbit[7]uril was immobilized on the surface of the sensing platform as an identification probe, which could selectively capture insulin according to the inherent properties of the protein N-terminal. Introducing the rigid molecule cucurbit[7]uril into the sensing interface could reduce the influence of the environmental parameters on the sensing system, which provides a reliable guarantee for the accurate detection of insulin. Furthermore, gold nanoclusters were modified by utilizing the molecular recognition properties of cucurbit[7]uril, and used as anode signal probes for ECL sensing platform. The macrocyclic molecules cucurbit[7]uril passivated the surface of the nanoclusters, inhibited the non-radiative relaxation and improved the physical stability of the luminophore, leading to a significant increase in the sensitivity and stability of the ECL probe. The ECL sensing platforms exhibited a linear range from 50.00 fg/mL to 100.0 ng/mL, with a detection limit of 5.44 fg/mL. This study revealed the critical role of cucurbit[7]uril in target recognition and signal amplification, extending the scope of supramolecular applications in ECL.

An amphiphilic [2]biphenyl-extended pillar[6]arene: Synthesis, controllable self-assembly in water and application in cell-imaging

Synthesis and functionalization of novel macrocyclic host molecules are important topics in supramolecular chemistry. In this work, the first amphiphilic [2]biphenyl-extended pillar[6]arene (AM-[2]BP-ExP6) was designed and synthesized with poly(ethylene glycol) chains as the hydrophilic tails and a rigid cavity as the hydrophobic core. Due to its amphiphilic nature, AM-[2]BP-ExP6 could self-assemble to stable fibers in water. What's more, AM-[2]BP-ExP6 could associate with quaternary ammonium modified tetraphenylethylene guest (QTPE) to form a 2:1 host-guest complex, accompanied by significant enhanced fluorescence. Interestingly, different like AM-[2]BP-ExP6, AM-[2]BP-ExP6⊃QTPE host-guest complex self-assembled into fluorescent particles with diameter about 310 nm, the obtained fluorescent particles can be further employed in living cell imaging.

Comparative DFT-D3 assessment of fluorogenic supramolecular interaction of naphthalene moiety location on new dibenzodiaza-crown ether macrocycles with C60

A family of dibenzodiaza-crown ether macrocyclic host molecules with naphthalene arms (Ln=L1-L4) were synthesized and characterized using IR, fluorescence (FL),1H, 13C NMR spectroscopy, elemental microanalysis, and mass spectrometry. The FL binding constant (KBH) measurements represented prominent selective supramolecular interactions for Ln (host) towards C60 (guest). The comparison of KBH values for (Ln=L1-L4) with C60 was executed, employing DFT calculations using the B97-D3 functional and 6-31G* basis set. These calculations unveiled excellent compatibility between the theoretical and experimental results of the binding constants, wherein the highest supramolecular interaction of L3 with C60 was explained in terms of better structural adjustment and more convenient electronic properties of the naphthalene pendant arms.

IR, UV-visible, NMR spectra and aromaticity of the covalent organic tetraoxa[8]circulene frameworks

In this paper, we explore the aromaticity, electronic, vibrational and NMR spectra of the novel tetraoxa[8]circulene-based covalent organic frameworks which were first synthesized in 2022 [Angew. Chem. Int. Ed. 61 (2022) e202116527] being predicted by quantum chemical modeling in 2014 [Phys. Chem. Chem. Phys. 16 (2014) 6555–6559]. Both studied 2x2 and 3x3 tetraoxa[8]circulene (TOC) oligomers represent polyaromatic systems consisting of 108π (2x2) and 168π (3x3) electrons in the outer perimeter with a global diatropic (“aromatic”) current; they includes also two types of internal rings: the cyclooctatetraene cores with 8π electrons and larger C16(CH4)O4 cavities with 28π electrons. Both internal rings provide local paratropic (“antiaromatic”) ring currents.The elongated π-conjugated system of the 2x2 and 3x3 TOC oligomers is responsible for the unique nature of photoinduced charge transfer and vibrational spectra, which obey strict selection rules within the D4h symmetry point group. The nature of photoinduced charge transfer was interpreted using visualization methods including charge density difference and transition density matrix. It was found that strong optical absorption around 500 nm is for the doubly degenerated S3(4) (1Eu) states, in which one pair of oppositely located anthracene fragments has an alternating distribution of holes and electrons, while in the other pair of anthracene fragments, the holes and electrons are mainly localized on the central benzene fragments and the ethylene bridges of adjacent furan rings, respectively. For both 2x2 and 3x3 TOC oligomers, the optical absorption strength for S1 and S2 states is vanished. The density functional calculations of 2x2 and 3x3 TOC models have also allowed us to make the assignment of all the observed lines in the IR and Raman spectra of experimental pTOC samples. We believe that the TOC oligomers represent a new-generation of macrocyclic host molecules in heterocirculene and supramolecular chemistry.

Light-responsive nanochannels based on the supramolecular host-guest system.

The light-responsive nanochannel of rhodopsin gained wider research interest from its crucial roles in light-induced biological functions, such as visual signal transduction and energy conversion, though its poor stability and susceptibility to inactivation in vitro have limited its exploration. However, the fabrication of artificial nanochannels with the properties of physical stability, controllable structure, and easy functional modification becomes a biomimetic system to study the stimulus-responsive gating properties. Typically, light-responsive molecules of azobenzene (Azo), retinal, and spiropyran were introduced into nanochannels as photo-switches, which can change the inner surface wettability of nanochannels under the influence of light; this ultimately results in the photoresponsive nature of biomimetic nanochannels. Furthermore, the fine-tuning of their stimulus-responsive properties can be achieved through the introduction of host–guest systems generally combined with a non-covalent bond, and the assembling process is reversible. These host–guest systems have been introduced into the nanochannels to form different functions. Based on the host–guest system of light-responsive reversible interaction, it can not only change the internal surface properties of the nanochannel and control the recognition and transmission behaviors but also realize the controlled release of a specific host or guest molecules in the nanochannel. At present, macrocyclic host molecules have been introduced into nanochannels including pillararenes, cyclodextrin (CD), and metal–organic frameworks (MOFs). They are introduced into the nanochannel through chemical modification or host–guest assemble methods. Based on the changes in the light-responsive structure of azobenzene, spiropyran, retinal, and others with macrocycle host molecules, the surface charge and hydrophilic and hydrophobic properties of the nanochannel were changed to regulate the ionic and molecular transport. In this study, the development of photoresponsive host and guest-assembled nanochannel systems from design to application is reviewed, and the research prospects and problems of this photo-responsive nanochannel membrane are presented.

Structure-Activity Relationship of the Thiacalix[4]arenes Family with Sulfobetaine Fragments: Self-Assembly and Cytotoxic Effect against Cancer Cell Lines.

Regulating the structure of macrocyclic host molecules and supramolecular assemblies is crucial because the structure–activity relationship often plays a role in governing the properties of these systems. Herein, we propose and develop an approach to the synthesis of the family of sulfobetaine functionalized thiacalix[4]arenes with regulation of the self-assembly and cytotoxic effect against cancer cell lines. The dynamic light scattering method showed that the synthesized macrocycles in cone, partial cone and 1,3-alternate conformations form submicron-sized particles with Ag+ in water, but the particle size and polydispersity of the systems studied depend on the macrocycle conformation. Based on the results obtained by 1H and 1H-1H NOESY NMR spectroscopy and transmission electron microscopy for the macrocycles and their aggregates with Ag+, a coordination scheme for the Ag+ and different conformations of p-tert-butylthiacalix[4]arene functionalized with sulfobetaine fragments was proposed. The type of coordination determines the different shapes of the associates. Cytotoxic properties are shown to be controlled by the shape of associates, with the highest activity demonstrated by thiacalix[4]arenes in partial cone conformation. This complex partial cone/Ag+ is two times higher than the reference drug imatinib mesylate. High selectivity against cervical carcinoma cell line indicates the prospect of their using as components of new anticancer system.